ID CREG1_HUMAN Reviewed; 220 AA. AC O75629; B2RDD4; Q8N9A3; DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 13-FEB-2019, entry version 143. DE RecName: Full=Protein CREG1; DE AltName: Full=Cellular repressor of E1A-stimulated genes 1; DE Flags: Precursor; GN Name=CREG1; Synonyms=CREG; ORFNames=UNQ727/PRO1409; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX PubMed=9710587; DOI=10.1128/MCB.18.9.5032; RA Veal E., Eisenstein M., Tseng Z.H., Gill G.; RT "A cellular repressor of E1A-stimulated genes that inhibits activation RT by E2F."; RL Mol. Cell. Biol. 18:5032-5041(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lymph, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 32-46. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally RT verified cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [8] RP SUBCELLULAR LOCATION, AND GLYCOSYLATION. RX PubMed=10815803; DOI=10.1038/sj.onc.1203529; RA Veal E., Groisman R., Eisenstein M., Gill G.; RT "The secreted glycoprotein CREG enhances differentiation of NTERA-2 RT human embryonal carcinoma cells."; RL Oncogene 19:2120-2128(2000). RN [9] RP INTERACTION WITH IGF2R, AND FUNCTION. RX PubMed=12934103; DOI=10.1038/sj.onc.1206670; RA Di Bacco A., Gill G.; RT "The secreted glycoprotein CREG inhibits cell growth dependent on the RT mannose-6-phosphate/insulin-like growth factor II receptor."; RL Oncogene 22:5436-5445(2003). RN [10] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-160; ASN-193 AND ASN-216. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 49-220, AND SUBUNIT. RX PubMed=16344469; DOI=10.1073/pnas.0505071102; RA Sacher M., Di Bacco A., Lunin V.V., Ye Z., Wagner J., Gill G., RA Cygler M.; RT "The crystal structure of CREG, a secreted glycoprotein involved in RT cellular growth and differentiation."; RL Proc. Natl. Acad. Sci. U.S.A. 102:18326-18331(2005). CC -!- FUNCTION: May contribute to the transcriptional control of cell CC growth and differentiation. Antagonizes transcriptional activation CC and cellular transformation by the adenovirus E1A protein. The CC transcriptional control activity of cell growth requires CC interaction with IGF2R. {ECO:0000269|PubMed:12934103, CC ECO:0000269|PubMed:9710587}. CC -!- SUBUNIT: Homodimer. Interacts with IGF2R; the interaction is CC dependent on glycosylation. {ECO:0000269|PubMed:12934103, CC ECO:0000269|PubMed:16344469}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10815803}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10815803, CC ECO:0000269|PubMed:19159218}. CC -!- SIMILARITY: Belongs to the CREG family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF084523; AAC34861.1; -; mRNA. DR EMBL; AY359071; AAQ89430.1; -; mRNA. DR EMBL; AK095456; BAC04550.1; -; mRNA. DR EMBL; AK315497; BAG37881.1; -; mRNA. DR EMBL; AL031733; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW90795.1; -; Genomic_DNA. DR EMBL; BC006786; AAH06786.1; -; mRNA. DR EMBL; BC008628; AAH08628.1; -; mRNA. DR CCDS; CCDS1262.1; -. DR RefSeq; NP_003842.1; NM_003851.2. DR UniGene; Hs.5710; -. DR PDB; 1XHN; X-ray; 1.95 A; A/B/C/D=49-220. DR PDBsum; 1XHN; -. DR ProteinModelPortal; O75629; -. DR SMR; O75629; -. DR BioGrid; 114332; 10. DR IntAct; O75629; 2. DR STRING; 9606.ENSP00000359540; -. DR GlyConnect; 1653; -. DR iPTMnet; O75629; -. DR PhosphoSitePlus; O75629; -. DR BioMuta; CREG1; -. DR EPD; O75629; -. DR jPOST; O75629; -. DR MaxQB; O75629; -. DR PaxDb; O75629; -. DR PeptideAtlas; O75629; -. DR PRIDE; O75629; -. DR ProteomicsDB; 50128; -. DR DNASU; 8804; -. DR Ensembl; ENST00000370509; ENSP00000359540; ENSG00000143162. DR GeneID; 8804; -. DR KEGG; hsa:8804; -. DR UCSC; uc001gel.4; human. DR CTD; 8804; -. DR DisGeNET; 8804; -. DR EuPathDB; HostDB:ENSG00000143162.7; -. DR GeneCards; CREG1; -. DR HGNC; HGNC:2351; CREG1. DR HPA; HPA056390; -. DR MIM; 618055; gene. DR neXtProt; NX_O75629; -. DR OpenTargets; ENSG00000143162; -. DR PharmGKB; PA26869; -. DR eggNOG; KOG3374; Eukaryota. DR eggNOG; ENOG4111WS9; LUCA. DR GeneTree; ENSGT00390000005914; -. DR HOGENOM; HOG000239875; -. DR HOVERGEN; HBG051115; -. DR InParanoid; O75629; -. DR OMA; GPHKVSA; -. DR OrthoDB; 1252017at2759; -. DR PhylomeDB; O75629; -. DR TreeFam; TF324680; -. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR EvolutionaryTrace; O75629; -. DR GeneWiki; CREG1; -. DR GenomeRNAi; 8804; -. DR PRO; PR:O75629; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000143162; Expressed in 238 organ(s), highest expression level in mammalian vulva. DR Genevisible; O75629; HS. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl. DR GO; GO:0048037; F:cofactor binding; IEA:InterPro. DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc. DR GO; GO:0008134; F:transcription factor binding; IEA:Ensembl. DR GO; GO:0007275; P:multicellular organism development; TAS:ProtInc. DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome. DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; TAS:ProtInc. DR Gene3D; 2.30.110.10; -; 1. DR InterPro; IPR014631; CREG. DR InterPro; IPR012349; Split_barrel_FMN-bd. DR PIRSF; PIRSF036911; CREG; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Direct protein sequencing; KW Glycoprotein; Growth regulation; Reference proteome; Secreted; Signal. FT SIGNAL 1 31 {ECO:0000269|PubMed:15340161}. FT CHAIN 32 220 Protein CREG1. FT /FTId=PRO_0000006203. FT CARBOHYD 160 160 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19159218}. FT CARBOHYD 193 193 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19159218}. FT CARBOHYD 216 216 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19159218}. FT CONFLICT 52 59 Missing (in Ref. 4; BAC04550). FT {ECO:0000305}. FT HELIX 55 65 {ECO:0000244|PDB:1XHN}. FT STRAND 67 74 {ECO:0000244|PDB:1XHN}. FT HELIX 78 80 {ECO:0000244|PDB:1XHN}. FT STRAND 84 90 {ECO:0000244|PDB:1XHN}. FT STRAND 104 107 {ECO:0000244|PDB:1XHN}. FT HELIX 112 119 {ECO:0000244|PDB:1XHN}. FT STRAND 122 128 {ECO:0000244|PDB:1XHN}. FT HELIX 129 131 {ECO:0000244|PDB:1XHN}. FT HELIX 134 138 {ECO:0000244|PDB:1XHN}. FT STRAND 149 158 {ECO:0000244|PDB:1XHN}. FT HELIX 161 163 {ECO:0000244|PDB:1XHN}. FT HELIX 164 174 {ECO:0000244|PDB:1XHN}. FT HELIX 176 180 {ECO:0000244|PDB:1XHN}. FT HELIX 183 185 {ECO:0000244|PDB:1XHN}. FT STRAND 188 200 {ECO:0000244|PDB:1XHN}. FT STRAND 202 205 {ECO:0000244|PDB:1XHN}. FT HELIX 211 216 {ECO:0000244|PDB:1XHN}. SQ SEQUENCE 220 AA; 24075 MW; 0DB95A1E4149CD7C CRC64; MAGLSRGSAR ALLAALLAST LLALLVSPAR GRGGRDHGDW DEASRLPPLP PREDAARVAR FVTHVSDWGA LATISTLEAV RGRPFADVLS LSDGPPGAGS GVPYFYLSPL QLSVSNLQEN PYATLTMTLA QTNFCKKHGF DPQSPLCVHI MLSGTVTKVN ETEMDIAKHS LFIRHPEMKT WPSSHNWFFA KLNITNIWVL DYFGGPKIVT PEEYYNVTVQ //